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Genetics
Genetics is the branch of biology which studies genes, genetic variation, and heredity in organisms. It was discovered by the Austrian friar Gregor Mendel in the late-19th century, as he discovered the concept of units of inheritance (now known as "genes") in organisms. Since then, geneticists have studied gene and cell structure, the study of DNA, and the study of gene editing and alteration (the improvement of genes, i.e. eugenics). Overview of Genetics Origins ]]The study of genetics originated during the 19th century. One of the early theorists, Jean-Baptiste Lamarck, argued that animals inherited their parents' traits. However, modern genetics begins with Gregor Mendel (who studied the traits of pea plants over several generations) and Charles Darwin (who devised the concepts of evolution and natural selection) in the late 19th century. The ideas of natural selection led to some prematurely concluding that it was also natural in human society to adapt to survive, leading to the rise of Social Darwinism and eugenics. Both of these movements, which were pioneered by the conservative white (in the United States, WASP) elites, would largely die out as a result of the Great Depression and World War II. Modern genetics: 1925 to 1960 ]]By the beginning of the 20th century, it was established that there were units of inheritance within the cell, these units somehoow held the information which guided the development of the organism (and were involved with the evolution of life on the planet), there were patterns to the inheritance of these units that followed some underlying guiding mathematical principle (Mendelian genetics), that some traits seemed to be complex in their inheritance through an interaction of many of the units with the environment (Francis Galton's theory of polygenetic inheritance), that these units of inheritance were located within the cell (most likely on the chromosomes, as per the Chromosome Theory of Inheritance), and that the idea of these units of inheritance was so powerful that this concept of the gene had influenced the social and political progams of nations. What was not known as what exactly the gene was and what it was made up of, how it contained the information of inheritance, how its information traveled from a parent to the offspring, how it changed and mutated, how it expressed the information, and how the gene was influenced by the environment. The period of time at the beginning of the 20th century is scientifically spectacular, and the answers to many of the questions started to emergy. Discovery of DNA ]]The quiet, educated physician Friedrich Miescher, who was interested in clotting and bacterial infections, especially pus. He decided to look into what it was made of, exposing it to chemicals. He found out that, in the pus, nucleic acid, and in the nucleus, there was a material that would precipitate out of the cells. He discovered a fluffly substance, which he called nuclein (now known as DNA). In 1928, Frederick Griffith discovered that in heat-killed, disease-causing bacteria, there was a factor which could change harmless bacteria into disease-causing bacteria, "bacterial transformation". Non-virulent bacteria could be transformed into virulent bacteria by the contact between the remnants of dead virulent bacteria with active harmless bacteria. For the first time, people were able to control a movement of chemicals holding units of inheritance. Griffith found that some molecule or molecules held the ability to transmit genetic information, but wondered what it was. Science showed that the cell was composed of many different classes of molecules - the molecules of life, sugars (carbohydrates), fats, proteins, and nucleic acids. Of the major classes, proteins were by far the most diverse. Proteins were in almost every function of the cells, and there were literally thousands of different types of proteins in the cell, doing almost every function in the cell, they were generally thought of as the "work horse" of the cell. They were enzymes, structural elements, hormones, and movers of other molecules. They were molecular components of the chromosomes (along with nucleic acid), and were generally believed to be the most likely molecular candidate to be the genetic material. ]] However, all of these theories changed when Oswald Avery decided to find out what exactly was Griffith's transforming agent; through isolating parts of the pathogen, he discovered that nucleic acid was the transformative agent. Erwin Chargaff wanted to learn more about the chemical nature of the molecule called DNA in New York City at Rockefeller University and at Columbia University, and he discovered that all DNA has the same type of sugar, that it has four nitrogen bases, that adenine is always equal to thymine (a=t) and that cytosine is equal to guanine (c=g), and that "a+t/g+c" will have different results for each species due to differing traits and ratios in each species. William Henry Bragg and his son Lawrence Bragg demonstrated that one could look at crystals in such a way that, if one shot an X-ray at them, they had their atoms in place, causing them to facture. The two of them figured out how to find the dots within a crystal, and they were able to make a guess as to the structure of the crystal, pioneering difraction studies; they shared the 1915 Nobel Prize. ]] Erwin Schrodinger wrote an inspiring book, What is Life? The Physical Aspect of the Living Cell in 1944 for the lay reader, seeing life as being a collection of molecules. He sought to discover the kind of molecule which contained infromation for the bdoy, and his book attracted the attention of scientists around the world. He postulated his theory of a master chemical - an aperiodic crystal - which could describe how cells could grow and how they could differentiate, which contained genetic information in its configuration of covalent chemical bonds, and which theoretically described the storage of genetic information. James Watson, Francis Crick, Maurice Wilkins, and Rosalind Franklin read Schrodinger's book, and Watson and Crick proposed the double helix structure of DNA based on X-ray diffraction experiments by Franklin and Wilkins. Franklin worked at the laboratory of brilliant New Zealander physicist and molecular biologist Wilkins in London, but they did not get along, as Wilkins sought to make the perfect DNA crystal, while Franklin took the most famous and beautiful X-ray picture ever taken. Wilkins considered Franklin his assistant instead of his co-worker, leading to rivalry. Meanwhile, Watson and Crick met each other as graduate students at Cambridge, and they went on to share an office and work together to study DNA. Watson and Crick studied X-ray diffraction, and Watson met with Wilkins, befriended him, and used Franklin's picture for futher studies. Watson knew that the photo was of a double helix, and he used Chargaff's theory to confirm it. There were also others interested in DNA, including Linus Pauling, another expert in crystalography. Pauling published his own paper on DNA structure, but it turned out to be wrong, as the structure was a triple helix, and he had the phosphates be in the middle, while the bases pointed out. Watson and Crick put a model together, but their first model was also wrong; their second model became the correct model of DNA. Watson and Crick received the 1962 Nobel Prize for Phsyiology or Medicine for their model. They believed that, in the DNA molecule, a template was stored, and Crick hypothesized that the adenine, thymine, guanine, and cytosine were arranged in a code, the genetic code. The DNA was arranged in a spiral stairacse fashion, and its Ts matched with As, while Cs matched with Gs; Schrodinger's theory that the crystal could reproduce itself was true in DNA, and it also had encoded messages; therefore, DNA was the master molecule of life. In DNA, errors in the information copying process can cause mutations. DNA is frequently being damaged, so the body utilizes repair mechanisms to save the DNA. In mismatch repair, special enzymes fix incorrectly paired nucleotides; a hereditary defect in one of these enzymes is associated with a form of colon cancer. In nucleotide excision repair, a nuclease cuts out a segment of a damaged strand, and the gap is filled in by DNA polymerase and ligase. In recombination, the DNA molecule can replicate itself. Mutations are one way to introduce differenes such as blue eyes in a sea of brown eyes, while nature uses the process of recombination (the exchange of genetic material between maternal and paternal chromosomes during the process of meiosis, first described by Thomas Hunt Morgan and his students). The DNA replication process starts when the continuous string of DNA is wrapped around histone molecules (which complexes with other histones). The result is the creation of the Chromatin fiber, which is coiled and looped again, leading to the creation of chromosome shapes. After the eight-hour process of DNA replication, each one of the chromosomes duplicates itself. Afterwards, the DNA forms spindles with spindle fibers on the metaphase plate; the cell then divides, the chromosomes pull away, and two new cells are formed, each with four chromosomes. This is the process of mitosis, which occurs in the production of skin, liver, and other bodily cells (somatic cells). Central dogma Francis Crick postulated the Central Dogma of genetics, arguing that the code in the DNA had to be translated to make proteins. Within 4-5 years, Watson and Crick worked out the code which determined which proteins could be made by which genes, and they came up with the process by which protein was made; the DNA is transcribed to RNA, which is translated into protein. Protein is made up of amino acids, of which there are 20 types. Amino acids can be linked together to make a protein, and the code in the DNA tells the cell what proteins to make; cells are made up of different kinds of proteins. Through the process of gene expression, genes can be turned on or off to make different cell types. Genes function as sequences of the DNA which can eventually make parts of proteins; proteins called histones are present in the DNA. The DNA-dependent, RNA-polymerase molecule is dependent on the DNA, making a strand of RNA in trying to copy the DNA in the "transcriptional process". Ribosomes bind to the messenger RNA, and the ribosome reads its code and produces a chain made up of amino acids. The transfer RNA molecule is created for each of the 20 amino acids, and there is redundancy in the code, with some RNA having more keys than others. The keys on the transfer RNA molecules find their messages on the message RNA, forming the beginning of the protein. The chain then folds into a 3D shape, forming a protein molecule. Amino acids have three-letter descriptions such as GAA and GAG for glucose, GGU, GGC, GGA, and GGG for glutanic acid, GAU and GAC for aspartame, and others. The codes for the amino acids are categorized by the same first two letters, with variable third letters. If there is a problem in the transfer of amino acids, there may be an error in the first two letters. As triplets, the codes do not overlap, with each of the triplets being independent of each other (degenerate) when positioned next to each other. The same genetic code, whether in a worm, a fly, a dog, or a cat, specifies that the amino acid would be in the specific protein, across all living creatures. Every living being works with the same genetic code. Polypeptide bonds string the amino acids together, forming the basic building blocks of proteins. Operon theory The scientists who discovered the relationship of genes to proteins and biochemical reactions were George Beadle and Edward Tatum, who were awarded the Nobel Prize in 1958. They demonstrated that genes controlled the production of enzymes which catalyzed the reactions in a biochemical pathway; they also created the idea of One Gene coding for the formation of One Protein. Xuring the 160s, another group of scientists, including Jacob and Monod, began to learn about gene expression. They questioned why all the cells of the body had the same genes (but some cells became heart cells, others lung cells, and others liver cells, etc.), and how a single fertilized cell could develop into a total organism. The answer was that different genes get turned on or off at different times, and the orchestrated gene expression determined which proteins were made and when they were made. The control of the entire development of an organism and the entire metabolism of the cells was primarily at the gene level. Jacob and Monod won the 1960 Nobel Prize for extending human knowledge of gene regulation through their "Operon theory", and they also started to learn about the genetic controls over development and cellular differentiation. Genes are often linked together by the enzyme pathways they want to work on; lactose is worked upon by an enzyme which breaks it apart; this enzyme is close to the enzyme that allows the lactose that comes into the cell, and next to another enzyme which makes lactose easy to cut up. The genes had to all be turned on or off at the same time, making bacteria efficient. The process by which it did so involved a repressor (which prevents RNA polymerase from sitting down) being activated by lactose. Lactose is made up of galactose and glucose (itself a mono-sacharide). After the glucose is used up, the bacteria seeks the lactose. The glucose is able to inactivate the repressor on the operon, which comes off, allowing for the RNA polymerase to set down and make all of the enzymes needed to break up the lactose, and free more glucose. Development In embrology, humans undergo a process called "ontogeny recapitulates phylogeny". This process shows the evolutionary presence of genes affecting development as one travels through the phylogenic tree of life; a human starts off as a fertilized egg, develops a fish-like embryonic stage (with gills and a tail), and develops into a human baby. Humans have genes which eradicate the tail, but some humans are born with gill-slits and smal tails; these are the vestiges of humanity's relationship to other primates such as monkeys and apes. If the process and its timing goes wrong, there are defects such as, in flies, legs appearing where antennae should be, or flies having four wings instead of one pair. Beings have adavism genes which can be activated, giving animals traits which their ancestors possessed; chickens may grow a tooth or a tail, could stand upright, or be tall through the activation of these genes, which were passed down to them through their dinosaur ancestors. Eggs and embyos have polarity, starting off with an egg and a sperm, which unite and form a zygote. The one cell finds out its purpose through inducer chemicals; a gradient of substances are set down and these substances induce the turning on or off of specific genes (via operons) at specific times to control embryonic development. In 2002, Sydney Brenner, H. Robert Horvitz, and John Sulston won the Nobel Prize in Medicine and Physiology by contributing to our understanding of the genetics of development, discovering that the adult C. elegans hermaphrodite contains exactly 959 cells. They came up with two competing models for the way brain cells determine their neural functions: the "European plan" and "American plan", named after European and American class mobility systems. The scientists' "European plan" stipulated that a mother cell with a specific function would create daughter cells with similar functions, while the "American plan" stipulated that, if a cell migrated to a different area, it could adopt the function of its neighboring visual cortex cells and develop new functions regardless of its genetic lineage. Other genes are starting to be discovered include housekeeping genes (which keep all clels alive and run the metabolism and catabolism of the cell), blueprint genes (which specify that a certain product is made for a critical function to operate well), and receipt genes (genes that get turned on or off in the proper sequence to control a process), all of which have been explored by Richard Dawkins. From the 1940s to the 1960s, scientists learned the structure of DNA (1953), how DNA replicates, to crack the genetic code, how DNA Codes for proteins, that chemicals and radiation can cause mutations such as cancer and birth defects, and gaining insight to the genetic control over development. During the World War II and Cold War eras, immigrant scientists such as Albert Einstein, Enrico Fermi, Werner Heisenberg, and Leo Szilard made important scientific innovations. Einstein, Fermi, and Szilard worked on the Manhattan Project, pioneering the use of feasible material from uranium to make atomic bombs which could be used against the Axis during World War II; the Germans demonstrated that uranium could be broken up. During the 1950s, Stanley Miller's experiment at Columbia University tried to recreate the molecular environment that was present on the Earth before life to see if these conditions were favorable to the spontaneous formation of life. The experiment showed that some of the basic building block molecules of proteins and nucleic acids could form under these conditions. The mixture of water, steam, lightning, and other natural resources could create amino acids, and the amino acids would eventually evolve into living beings. During the 1960s, new innovations such as birth control pills, advances in heart/lung machines, in vitro fertilization, test tube babies, the first heart transplants, prenatal diagnosis of genetic diseases, cloning of frogs, the 1969 moon landing occurred, revolutionizing modern science. The 1960s also saw the presidencies of John F. Kennedy, Lyndon B. Johnson, and Richard Nixon in the United States, the rise of Fidel Castro, the Bay of Pigs invasion, and the Cuban Missile Crisis in Cuba, the Berlin Wall crisis, the Vietnam War and its escalation, the assassinations of John F. Kennedy, Robert F. Kennedy, and Martin Luther King, Jr., the rise of social movements, and the proliferation of recreational drug use. Human Genetics ]]Archibald Garrod, a noted physician in England during the early 1900s, made the first association of a disease state in humans that followed Mendelian inheritence; he did so through collecting clinical information on several families that showed the urine of newborns turning black. He determined that an intermediate in biochemical pathway of phenylalanine-homogentisic acid accumulated in these patients and followed Mendel's laws of recessive inheritence. Many of these children were offspring of first cosin marriages; Garrod discovered the inborn errors of metabolism. Types of genetic diseases Soon, several diseases (approximately 10,000) that followed Mendelian gneetics became known, including autosomal recessive, autosomal dominant, and sex-linked diseases. There were also those that were chromosomal (trisomy, monosomy, structural rearrangements), and those that were the result of interactions between many genes (multifactorial). These diseases are, for the most part, individually very rare, so it became a necessity for the medical profession to catalogue and characterize each of them according to their genetics, symptoms, treatments, and any other important information. Victor McKusick was considered to be "the Father of American Medical Genetics." An identical twin of a lawyer, he was a professor at Johns Hopkins Hospital in Baltimore, and he was a proponent of the mapping of the human genome due to its use for studying congenital diseases; he was well-known for his studies of the Amish and, what he called, "little people" due to the commonality of birth defects in both groups due to first-cousin interbreeding. McKusick put together a catalogue of diseases, which consistently expanded. There are many different types of professionals who come together to prevent, treat, and cure genetic diseases. Cases usually fall into either postnatal or prenatal genetics cases. When geneticists receive cases, their first step is to make a pedigree, a detailed history of the subject's family. The pedigree can show if any diseases fit an inheritance pattern in the family through a detailed chart. It is possible for there to be autosomal dominant disorders, in which some diseases have a 50% chance of occurring. Achondroplasia (dwarfism) is a common genetic condition, as it is autosomal dominant, and it affects males and females. Over 80% of achondroplasia cases have parents with normal stature, and such parents have a low risk of having another child with the mutation. Huntington's disease (which destroys the brain) is almost always inherited, and the chances of acquiring it increase with each generation. Marfan's syndrome, an autosomal-dominant connective tissue disorder, results in an increase in the protein TGFB (transforming growth factor beta), which causes tissue problems throughout the body and an incredibly long wingspan. 1 in 20 Caucasian people are carriers of cystic fibrosis, another major illness, which includes mucus blocking the airway and other tubes in the body; 1/1,600 children can spontaneously acquire cystic fibrosis. There is no cure or a way to prevent the disease, and the average life span is approximately 35 years; death is usually caused by lung complications. Sickle-cell anemia, an autosomal recessive disorder (a mother carrier passes down a disease to a child), affects the beta chains of hemoglobin, which is made up of two alpha chains and two beta chains. In the disease, people have just one alteration in the genes which makes the beta chains, substituting, in the number six position, a valine amino acid for the glutamic acid. The hemoglobin becomes sticky, forming a fiber which distorts the shape of the red blood cell in a sickle shape, ultimately being destroyed due to deoxygenation. When a person has a decreased number of red blood cells, a person cannot metabolize as well, exercise as well, or have enough oxygen. Organs can also be clotted by red-blood cells, a dangerous occurrence. People that are carriers of the disease have a number of defective cells, making them inhospitable to malaria-carrying mosquitoes. The heterozygote is resistant to the malarial parasite which kills a large number of people each year in Africa, and the heterozygote has a permanent advantage and a high fitness. Duchene's muscular dystrophy is caused by a gene present on the X-chromosome, and female carriers can transmit the disease to half of their sons. It is the biggest gene in the genome, occupying more than 1% of the active DNA on the chromosome, and consisting of 1.5 million base pairs (including informational exons and the introns, which have to be cut out). In muscular dystrophy, a significant portion of the gene is missing. The gene makes the dystrophin protein to serve as a buffer, holding everything in the muscle together. When the molecule is destroyed, other proteins are destroyed, and the muscle tissue starts to decrease. Some diseases cause a smaller amount of deletion, meaning that the situation is better than other cases. Becker's muscular dystrophy is less effective than Duchene's, and some drugs can convert Duchene's muscular dystrophy into Becker's, modifying the gene to improve the person's situation. In a rare case, mitochondria can malfunction, turning out less ATP (a vital energy molecule) than it should. If a female has a mitochondrial trait, all of her offspring inherit it; for men, it is the opposite. Only one allele is present in each individual, so dominance is not an issue. Category:Genetics Category:Biology